The long term objectives of our NCI-supported research efforts are to use chromosome aberrations in lymphocytes as sensitive endpoints to study the mechanisms by which high-LET radiations of widely different energies induce genetic damage in human cells and the extent to which DNA damage that leads to chromosome aberrations can be protected by radioprotective chemicals that have different mechanism of action. If soft neutron beams become available at RARAF, we propose to extend the studies to include neutrons having energies of less than 50 keV. Our specific aims will be: 1) To develop in vitro dose response curves for all classes of hromosome aberrations induced in human lymphocytes exposed to soft neutrons of varying energies and to derive estimates of the relative biological effectiveness (RBE) of soft neutrons in inducing pro pt cytogenetic damage in non-cycling human cells. 2) To produce a detailed profile of observed aberration types and to use the ratios of chromosomal interchanges:interchanges, dicentric:polycentrics, and exchanges:deletions as endpoints to determine whether the spectrum of chromosomal damage induced by soft neutrons is different than observed for fast, monoenergetic neutrons. 3) To derive estimates of the RBE for genomic detriment induced in the surviving fraction of irradiated cells by evaluating symmetrical aberrations in cells in their second or subsequent in vitro mitosis. 4) To determine the extent to which DNA damage induced by recoil protons that travel on average less than 0.5 microns can be protected by DMSO, a radioprotective chemical that selectively scavenges OH radicals, or by the aminothiol, WR-1065, which provides protection by several mechanisms.